Many environmental changes impact sleep, such as exposure to drugs, social isolation, and varying temperatures. Caffeine is a neuromodulator that is self-administered worldwide. We are investigating its effects on a set of 39 inbred lines with extreme long- and short-sleeping phenotypes. Aim 1. We are in the process of developing dose response curves for caffeine based on concentrations previously reported in the literature. Aim 2. We will measure sleep and activity parameters in a group of inbred flies that we developed from an artificial selection experiment. Nineteen of the lines are extreme long sleepers; 20 are short sleepers. We will perform gene expression studies on the effects of drug exposure on sleep and compare it to sleep under normal conditions. We will identify those gene networks that are robust across environments, and those gene networks that are plastic and perhaps unique to each environment.